Lymphomas and lymphoproliferative lesions developing under cyclosporin therapy.
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Clinical Trials as Topic↗
Biomedical subjects
T Beveridge
Publications and source records attributed to T Beveridge.
[Steroid-free treatment of renal transplant patients with cyclosporin A. A European multicentre study].
In a multicentre trial conducted in eight European centres, 232 recipients of cadaveric renal allografts were randomly allocated to receive either cyclosporin A (CyA, 117 patients) or azathioprine and steroids (control, 115 patients) for immunosuppression. After a follow-up period of up to eleven months, graft survival probability estimates are 73% in the CyA group and 53% in the control group. Two deaths have occurred In the CyA group and seven in the control group. 82% of the CyA group with functioning grafts are receiving CyA alone, 17% have been changed to azathioprine and steroids and one patient is receiving prednisolone in addition to CyA; 27% have never received steroids. At six months post-transplant renal function is similar in patients receiving CyA and in those receiving azathioprine and steroids. On the basis of these preliminary results CyA appears to be more effective than conventional immunosuppression and avoids the necessity of long-term steroid therapy.
Adult↗
Cyclosporin A: correlation between HPLC and RIA serum levels.
Serum levels of cyclosporin A were analysed in parallel with an HPLC and a RIA method for six patients who received repeated intramuscular and oral doses of this immunosuppressive drug after bone marrow transplantation. A good correlation was found between both methods with a similar time course of the serum curves. Due to cross-reacting metabolites, the values from the RIA assay were on average 30 to 100% higher than with the HPLC assay which is specific for the parent drug.
Administration, Oral↗
Effects of age and smoking on the pharmacokinetics of pindolol and propranolol.
1 Pharmacokinetic investigations were carried out in a group of 32 ambulant normal male volunteers in order to determine the effect of age and smoking on steady-state plasma levels of pindolol and propranolol. There were four groups of 8: young non-smokers (YNS), young smokers (YS), old non-smokers (ONS) and old smokers (OS). Each subject received, in a randomized cross-over sequence, 5 mg pindolol and 80 mg propranolol three times daily for 2 days with an interval of at least 14 days between the two treatment periods. 2 Neither age nor smoking was shown to have any influence on the time to reach a peak plasma level after pindolol or propranolol. Age, on the other hand, significantly increased the peak plasma levels and the areas under the plasma concentration time curves, and decreased the elimination rate constants, the differences between the age groups being more pronounced for propranolol than for pindolol. No effect of smoking on these parameters was observed. 3 Differences were found between pindolol and propranolol in respect of time to reach a peak plasma level, peak plasma levels and area under the plasma concentration time curves in the groups ONS and YS when related to the YNS control group. Changes observed (with the exception of the time to reach a peak level) tended to be less for pindolol and were considered to be of little clinical relevance.
Adult↗
Influence of smoking and age on pharmacokinetics of beta-receptor blockers.
The influence of age and smoking on pharmacokinetics of pindolol and propranolol was investigated. Although there was a statistically significant difference in certain pharmacokinetic parameters (maximum plasma concentration, area under the curve, elimination constant and elimination half-life) between elderly patients (more that 60 years) and young persons (20-30 years) no significant differences were found as far as smoking and nonsmoking is concerned. This is in contrast with some reports in the literature. The higher plasma concentrations of both investigated drugs may be the result of a decreased metabolism of propranolol in older persons, in a decreased hepatic blood flow and a decreased renal elimination. Because of the lower sensitivity of beta-receptors in old persons, the higher plasma concentrations of beta-receptor blockers in this group of patients should not result in a diminished dose of the investigated beta-receptor blockers in the elderly.
Adrenergic beta-Antagonists↗
Effects of fluproquazone on platelet aggregation in man.
Turbidimetric investigations on platelets from healthy volunteers have shown inhibitory effects of 4-(p-fluorophenyl)-1-isopropyl-7-methyl-2(1H)-quinazolinone (fluproquazone) and acetylsalicylic acid (ASA) on both the extent and the velocity of aggregation induced by collagen. The threshold concentration of arachidonic acid needed to induce aggregation was also raised after fluproquazone was given to the donors. Whereas the inhibitory effects of fluproquazone disappear within 24 h, the qualitatively similar effects of ASA are much longer lasting (72--96 h). There is no evidence for enhancement of the effects of fluproquazone following four days of administration (100 mg t.i.d.).
Adult↗
High-performance liquid chromatographic determination of cyclosporin A in human plasma and urine.
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Administration, Oral↗
High resolution microchemical analysis using soft X-ray lithographic techniques.
High resolution x-ray lithographic studies of cells from chick embryo hearts dried by the CO2 critical point method have been made with soft x-ray radiation of different wavelengths. A marked difference in the relief replica in polymethyl methacrylate (PMMA) resulting from the differential absorption by the dried cells of carbon K alpha radiation at 4.48 nm and broad band synchrotron radiation (SR) with lambda is greater than 1.5 nm demonstrates the potential usefulness of the technique in making high resolution (approximately or equal to 10 nm) chemical identification of the constitutents which make up the various parts of the cell.
Animals↗
Absolute bioavailability of digoxin tablets.
Ten healthy male volunteers each received 0.5 mg digoxin orally and i.v. in a randomised, cross-over sequence with at least two weeks between doses. Plasma concentration and cumulative urinary excretion of digoxin were measured up to 6 and 144 h, respectively, after administration using a radioimmunoassay method. Absolute bioavailability (i.e. the percentage absorption from tablets compared to i.v. injection) was calculated by four methods: by comparing areas under plasma concentration/time curves (AUC) up to 6 h and to infinity, also by comparing cumulative urinary excretion up to 144 h (t max.) and to infinity. The mean of the two extrapolated values for the absolute bioavailability of digoxin (Sandoz) tablets is 78%.
Administration, Oral↗
[Methodological contribution to the controlled measurement of platelet aggregation].
Collagen-induced platelet aggregation was investigated in healthy volunteers under well defined experimental conditions. The Born aggregometer was used and the two parameters studied were the maximum amount and velocity of aggregation. Under these experimental conditions no significant differences in measurements on 3 consecutive days were found. In addition, identical results were obtained in the same volunteers 4 and 8 weeks following the first experimental period. This experimental procedure was therefore used to test a new nonsteroid anti-inflammatory agent, RU 43-715, for its effect on platelet aggregation. Furthermore, a controlled crossover study using 3 different substances was performed. In the light of the results in the present study, controlled studies on platelet aggregation can be performed even over on even longer period of time under the experimental conditions described.
Anti-Inflammatory Agents↗
Pharmacokinetic study with synthetic salmon calcitonin (Sandoz).
18 patients randomly divided into 3 groups of six each received 35 mug (140 M.R.C. Units) of synthetic salmon calcitonin intravenously, intramuscularly or subcutaneously. Plasma and urin concentrations were determined using the radioimmunoassay method. There was a rapid distribution phase of ca. 12 minutes after intravenous injection then an elimination half-life of 1.1 hours. The volume of distribution was 11 litres. The invasion half-life after intramuscular and subcutaneous administration was 12 and 11 minutes respectively and the elimination half-lives 1 and 1.5 hours, respectively. The bioavailability of the intramuscular and subcutaneous forms was found to be 66 and 71% respectively when areas under their plasma concentration/time curves were compared with the intravenous area.
Adolescent↗
Bioavailability studies with Digoxin-Sandoz and Lanoxin.
Various brands of digoxin tablets, and even different batches of one brand, may differ greatly in bioavailability. Digoxin-Sandoz tablets have been compared with Lanoxin manufactured between 1969 and 1972 and after May 1972. Comparisons were also made between and within batches of Digoxin-Sandoz tablets. Three separate cross-over studies were conducted involving a total of 20 volunteers. Digoxin-Sandoz tablets were shown to have a constant bioavailability and to produce plasma concentrations very similar to ""new'' Lanoxin. Storage for 2 years of one batch of Digoxin-Sandoz did not alter the bioavailability. Particle size was shown to influence bioavailability. Care should be exercised when plasma data alone are interpreted as an index of bioavailability. Measures of bioavailability based on plasma data obtained up to 6 h after administration differed from those based on cumulative urinary excretion data (in this study by a factor of about 2), which can lead to the belief that a difference in bioavailability is much greater than is actually the case. Data from cumulative urinary excretion, collected over a sufficiently long period of time, are likely to be the most reliable method for determining the bioavailability of a substance such as digoxin.
Adult↗
Comparison of azathioprine, cyclophosphamide, and gold in treatment of rheumatoid arthritis.
Azathioprine, cyclophosphamide, and gold have been compared under double-blind conditions in the treatment of relatively early rheumatoid arthritis. Over 18 months the two "immunosuppressive" agents produced clinical improvement comparable to that achieved with gold, and they also facilitated a reduction in the dosage of corticosteroids and retarded radiological joint deterioration. Drug management was easiest with azathioprine. Cyclophosphamide was perhaps marginally the most effective drug but it produced azoospermia in males. If the long-term hazards of malignancy and mutagenesis prove to be acceptable then the anti-proliferative agents provide a useful alternative to gold therapy and can with advantage be given relatively early in the course of rheumatoid arthritis.
Adult↗
Bioavailability of digoxin.
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Biotransformation↗
Transfer of information about intake of drugs by patients referred to medical units.
The efficiency of the transfer of information among doctors about current drug therapy was examined in emergency, waiting list, and outpatients. Communication about the patient's recent medical history was established with the practitioner in 551 of 559 patients referred (99%). Four hundred and ninety-eight patients (89%) were currently taking 1,557 drugs either supplied by prescription or taken as self-medication. In 314 patients (56%) some information was supplied by the practitioner about 555 drugs (36%). Six hundred and thirteen (61%) of the 1,002 drugs not mentioned by the practitioner were drugs supplied by prescription, mainly hypnotics, sedatives, and analgesics. The transfer of information was unsatisfactory about drugs taken as self-medication and about the allergic status of patients.If iatrogenic disease due to drug therapy is to be recognized or prevented the communication of information about drugs must be improved.
Adolescent↗
The quantitative estimation of the activity of fourteen analogues of the neurohypophysial hormones on stripes of mammary gland in vitro.
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Animals↗
[Initial clinical experiences in the treatment of chronic polyarthritis with a new monokine release inhibitor].
Cytokines such as Interleukin-1 (IL-1) are important modulators of the cell-mediated immune response and play a paramount role in inflammatory autoimmune disease. We report on preliminary clinical experiences with a new, tricyclic substance [( 10-Methoxy-4H-benzo[4,5]cyclo-hepta-[1,2-b]thiophene-4- ylidene]acetic acid, MW 284), which inhibits the release of interleukin-1 alpha and -beta from cultured murine macrophages or human mononuclear cells. The study included 12 patients (rheumatoid arthritis, n = 9; hemochromatotic arthropathy, n = 1; psoriatic arthropathy, n = 1; seronegative spondylarthropathy, n = 1). Eight patients were treated for a total of 8 weeks, receiving a median dose of 800 mg/d of the substance. Due to significant clinical benefits, two patients continued for a total of six months. Administration of the drug was discontinued in two patients because of severe urticaria and lack of compliance, respectively. Four out of 10 patients showed clinical improvement according to Ritchie-Index, pain score, ESR and CRP. Side effects were diffuse gastrointestinal symptoms (4/12), temporary impairment of liver function (4/12) and allergic skin reactions (3/12).
Anti-Inflammatory Agents, Non-Steroidal↗
[Dihydrocyclosporin D--a new immunosuppressive?].
The first preliminary clinical results with a new Cyclosporin derivative (Dihydrocyclosporin-D) are reported. The compound has no obvious nephrotoxic effect; but it exhibits a hepatotoxic effect, and frequently leads to hypertension. The clinical efficiency cannot yet be judged with certainty.
Blood Pressure↗